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The molecular targets of resveratrol
Open accessAbstract
Resveratrol has emerged in recent years as a compound conferring strong protection against metabolic, cardiovascular and other age-related complications, including neurodegeneration and cancer. This has generated the notion that resveratrol treatment acts as a calorie-restriction mimetic, based on the many overlapping health benefits observed upon both interventions in diverse organisms, including yeast, worms, flies and rodents. Though studied for over a decade, the molecular mechanisms governing the therapeutic properties of resveratrol still remain elusive. Elucidating how resveratrol exerts its effects would provide not only new insights in its fundamental biological actions but also new avenues for the design and development of more potent drugs to efficiently manage metabolic disorders. In this review we will cover the most recent advances in the field, with special focus on the metabolic actions of resveratrol and the potential role of SIRT1 and AMPK. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.
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“Moreover, RSV is a well-known activator of SIRT1 and our previous study also found that RSV improved hepatic steatosis partially by inducing autophagy via the SIRT1 signaling pathway in vitro and in vivo (36–38).”
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“Moreover, RSV is a well-known activator of SIRT1 and our previous study also found that RSV improved hepatic steatosis partially by inducing autophagy via the SIRT1 signaling pathway in vitro and in vivo (36–38).”
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“However, despite producing an ex vivo increase in mitochondrial respiration that may be dependent of its ability to increase AMPK activity (Kulkarni and Cantó, 2015)”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Kulkarni and Cantó, 2015
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“tent declines to the levels thatmight compromise SIRT1 activity [37,38].”
BackgroundRapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531 · cited 3×
“mTOR complexes 1 and 2 (mTORC1 and mTORC2), the mTOR kinase plays a key role in several pathways involved in cancer and metabolic diseases [121].”
BackgroundInfluentialResveratrol Acts as a Mixed Agonist/Antagonist for Estrogen Receptors α and β*
Bowers, J. L., Tyulmenkov, V. V., Jernigan, S. C., & Klinge, C. M. (2000) · Endocrinology · doi:10.1210/endo.141.10.7721 · Cited by 527
Tsai, S., Lin‐Shiau, S., & Lin, J. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702357 · Cited by 511 · cited 1×
“Initial hypothesis suggested that Rsv might either reduce NF-κB nuclear presence [111] or interfere with the transcriptional activity [112].”
BackgroundMultiple molecular targets of resveratrol: Anti-carcinogenic mechanisms
Athar, M., Back, J. H., Kopelovich, L., Bickers, D. R., & Kim, A. L. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.01.018 · Cited by 462
Inhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals
Zheng, J., & Ramirez, V. D. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703397 · Cited by 453 · cited 1×
“Themost likely mechanism bywhich Rsv could activate AMPK relies on the ability of Rsv and related polyphenols (such as piceatannol and quercetin) to directly bind and inhibit the mitochondrial F1F0-ATPase/ATP synthase (Complex V), thus impairing ATP production [72,73].”
BackgroundSirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
Boily, G., Seifert, E. L., Bevilacqua, L., He, X. H., Sabourin, G., Estey, C., Moffat, C., Crawford, S., Saliba, S., Jardine, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001759 · Cited by 444 · cited 1×
“adaptations, including the effect of CR on longevity [41,42].”
BackgroundTargeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433 · cited 5×
“time frames (several hours) in order to drive SIRT1 activation (discussed in [25]).”
BackgroundInfluentialSelf-citationAlmeida, L., Vaz‐da‐Silva, M., Falcão, A. C., Soares, E., Costa, R., Loureiro, A. I., Fernandes‐Lopes, C., Rocha, J., Nunes, T., Wright, L. C., et al. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200800177 · Cited by 427 · cited 1×
“plasma are either not detectable or clearly below the micromolar range [19,20], as used in vitro.”
MethodAMP-activated protein kinase and its downstream transcriptional pathways
Cantó, C., & Auwerx, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0454-z · Cited by 421 · cited 2×
“For example, PGC-1α is one well-established target of SIRT1 that acts as a master orchestrator of mitochondrial biogenesis [47].”
BackgroundSelf-citationA Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span
Viswanathan, M., Kim, S. K., Berdichevsky, A., & Guarente, L. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.017 · Cited by 420
Resveratrol: Its Biologic Targets and Functional Activity
Pervaiz, S., & Holme, A. L. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2412 · Cited by 415 · cited 1×
“in a number of cell lines following Rsv treatment (see [95] and [98]), also supporting the Rsv chemopreventive activity.”
BackgroundCaloric restriction, SIRT1 and longevity
Cantó, C., & Auwerx, J. (2009) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.03.008 · Cited by 395
Self-citationMechanism of inhibition of bovine F 1 -ATPase by resveratrol and related polyphenols
Gledhill, J. R., Montgomery, M. G., Leslie, A. G. W., & Walker, J. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706290104 · Cited by 386 · cited 1×
“Themost likely mechanism bywhich Rsv could activate AMPK relies on the ability of Rsv and related polyphenols (such as piceatannol and quercetin) to directly bind and inhibit the mitochondrial F1F0-ATPase/ATP synthase (Complex V), thus impairing ATP production [72,73].”
BackgroundAnti-Inflammatory Responses of Resveratrol
Das, S., & Das, D. K. (2007) · Inflammation & Allergy - Drug Targets · doi:10.2174/187152807781696464 · Cited by 383 · cited 1×
“This way, Rsv has been shown to dramatically reduce COX-2 transcription by the combined downregulation of the Akt, MAPK and NF-κB pathways [100,101].”
BackgroundCalorie restriction and cancer prevention: metabolic and molecular mechanisms
Longo, V. D., & Fontana, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.11.004 · Cited by 378 · cited 1×
“Importantly, CR is an intervention that heavily protects against cancer development in rodents [8].”
BackgroundMagyar, K., Halmosi, R., Pálfi, A., Fehér, G., Czopf, L., Fulop, A., Battyány, I., Sümegi, B., Tóth, K., & Szabados, E. (2012) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-2011-1424 · Cited by 364
Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential
Shankar, S. (2007) · Frontiers in bioscience · doi:10.2741/2432 · Cited by 343 · cited 1×
“in a number of cell lines following Rsv treatment (see [95] and [98]), also supporting the Rsv chemopreventive activity.”
BackgroundGerhart‐Hines, Z., Dominy, J. E., Blättler, S. M., Jedrychowski, M. P., Banks, A. S., Lim, J.-H., Chim, H., Gygi, S. P., & Puigserver, P. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.12.005 · Cited by 336
PKA phosphorylates and inactivates AMPKα to promote efficient lipolysis
Djouder, N., Tuerk, R. D., Suter, M., Chiabotti, P. S., Thali, R. F., Scholz, R., Vaahtomeri, K., Auchli, Y., Rechsteiner, H., Brunisholz, R., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.339 · Cited by 285 · cited 1×
“might trigger AMPK activation [106–108], PKA has also been reported to directly phosphorylate and negatively influence AMPK activity [109].”
BackgroundCalorie Restriction: Is AMPK a Key Sensor and Effector
Cantó, C., & Auwerx, J. (2011) · Physiology · doi:10.1152/physiol.00010.2011 · Cited by 282
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“dose-dependently improve endothelium-dependent vasodilatation [15].”
Kundu, J. K., Shin, Y. K., Kim, S. H., & Surh, Y. (2006) · Carcinogenesis · doi:10.1093/carcin/bgi349 · Cited by 275 · cited 1×
“This way, Rsv has been shown to dramatically reduce COX-2 transcription by the combined downregulation of the Akt, MAPK and NF-κB pathways [100,101].”
Ashikawa, K., Majumdar, S., Banerjee, S., Bharti, A. C., Shishodia, S., & Aggarwal, B. B. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.11.6490 · Cited by 244
Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action
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“phytoestrogenic action of Rsv could support a chemoprotective role in breast cancer, there is also evidence suggesting possible adverse effects [132], likely depending on the distinctive patterns of ERα and ERβ expressions in different cell types.”
BackgroundStimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK
Breen, D. M., Sanli, T., Giacca, A., & Tsiani, E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.06.104 · Cited by 217 · cited 3×
“Similarly Rsv triggered skeletal muscle glucose transport in an AMPKdependent manner [62].”
BackgroundMattison, J. A., Wang, M., Bernier, M., Zhang, J., Park, S. S., Maudsley, S. R., An, S. S., Santhanam, L., Martin, B., Faulkner, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.018 · Cited by 206
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“plasma are either not detectable or clearly below the micromolar range [19,20], as used in vitro.”
MethodSirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction
Schenk, S., McCurdy, C. E., Philp, A., Chen, M. Z., Holliday, M. J., Bandyopadhyay, G. K., Osborn, O., Baar, K., & Olefsky, J. M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58554 · Cited by 197 · cited 1×
“Similarly, basal AMPK activity in the skeletal muscle seems unaffected by SIRT1 deletion [49,87,88].”
BackgroundResveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity
Maccarrone, M., Lorenzon, T., Guerrieri, P., & Finazzi‐Agrò, A. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00630.x · Cited by 194 · cited 1×
“In addition, Rsv has also been described to inhibit lipooxygenases (LOX) activity [102,103],”
BackgroundPatel, K. R., Andreadi, C., Britton, R. G., Horner‐Glister, E., Karmokar, A., Sale, S., Brown, V. A., Brenner, D. E., Singh, R., Steward, W. P., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005870 · Cited by 193 · cited 1×
“human colorectal cells into stable sulfate-conjugated forms, which would then gradually regenerate into the parental compound, providing the beneficial effects in vivo [21].”
BackgroundGarcia-Roves, P. M., Osler, M. E., Holmström, M. H., & Zierath, J. R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805078200 · Cited by 190 · cited 1×
“Finally, the significant effects of Rsv onmitochondrial biogenesis in the skeletal muscle closely mimic those observed by treatment with AMPK agonists [80] or AMPK gain-of-function models [81], but were not observed in models where SIRT1 was moderately overexpressed [56,82,83].”
BackgroundPhilp, A., Chen, A., Lan, D., Meyer, G. A., Murphy, A. N., Knapp, A. E., Olfert, I. M., McCurdy, C. E., Marcotte, G. R., Hogan, M. C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.261685 · Cited by 184 · cited 1×
“Similarly, basal AMPK activity in the skeletal muscle seems unaffected by SIRT1 deletion [49,87,88].”
BackgroundResveratrol Inhibits mTOR Signaling by Promoting the Interaction between mTOR and DEPTOR
Liu, M., Wilk, S. A., Wang, A., Zhou, L., Wang, R.-H., Ogawa, W., Deng, C., Dong, L., & Liu, F. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.169284 · Cited by 181 · cited 4×
“Recent studies have also demonstrated that Rsv inhibits mTOR signaling via a SIRT1-independent mechanism [122] and that it represses protein synthesis [123].”
BackgroundInfluentialResveratrol: From Basic Science to the Clinic
Cucciolla, V., Borriello, A., Oliva, A., Galletti, P., Zappia, V., & Ragione, F. D. (2007) · Cell Cycle · doi:10.4161/cc.6.20.4815 · Cited by 174
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Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes
Viswanathan, M., & Guarente, L. (2011) · Nature · doi:10.1038/nature10440 · Cited by 166
Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells
Suchankova, G., Nelson, L. E., Gerhart-Hines, Z., Kelly, M., Gauthier, M.-S., Saha, A. K., Ido, Y., Puigserver, P., & Ruderman, N. B. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.130 · Cited by 162 · cited 2×
“Surprisingly, Rsv led to AMPK activation within minutes inmost cell lines tested, including hepatic and cultured skeletal muscle cell models [45,62,69,70] much faster than generally required for SIRT1 activation.”
BackgroundInhibition of mammalian S6 kinase by resveratrol suppresses autophagy
Armour, S. M., Baur, J. A., Hsieh, S. N., Land-Bracha, A., Thomas, S. Μ., & Sinclair, D. A. (2009) · Aging · doi:10.18632/aging.100056 · Cited by 160 · cited 1×
“Interestingly, Rsv has also been found through an in vitro screen to act as a direct inhibitor of p70S6K [126], a key downstream target of the mTOR pathway regulating autophagy and protein translation rates, albeit at an IC50 of 25 μM[126], which is higher than the lowmicromolar concentrations at which Rsv enhances AM…”
BackgroundResveratrol is a class IA phosphoinositide 3-kinase inhibitor
Fröjdö, S., Cozzone, D., Vidal, H., & Pirola, L. (2007) · Biochemical Journal · doi:10.1042/bj20070236 · Cited by 158 · cited 3×
“and colleagues unveiled that Rsv could inhibit PI3K signaling independently of SIRT1 [118].”
BackgroundInfluentialWang, Z., Zou, J., Cao, K., Hsieh, T., Huang, Y., & WU, J. M. (2005) · PubMed · Cited by 152
Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle
Kelly, M., Gauthier, M., Saha, A. K., & Ruderman, N. B. (2009) · Diabetes · doi:10.2337/db08-1293 · Cited by 151
Distinct roles of IκB proteins in regulating constitutive NF-κB activity
Tergaonkar, V., Correa, R. G., Ikawa, M., & Verma, I. M. (2005) · Nature Cell Biology · doi:10.1038/ncb1296 · Cited by 148
Deng, J.-Y., Hsieh, P., Huang, J., Lu, L., & Hung, L. (2008) · Diabetes · doi:10.2337/db07-1750 · Cited by 147 · cited 1×
“In fact, while most data suggests that Rsv increases skeletal muscle glucose uptake [44,59,60], even in an acute fashion [61,62], SIRT1 transgenesis in the muscle does not affect insulin action [63].”
BackgroundOmar, B. A., Zmuda‐Trzebiatowska, E., Manganiello, V. C., Göransson, O., & Degerman, E. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.01.015 · Cited by 141
Resveratrol inhibits NF-kB signaling through suppression of p65 and IkappaB kinase activities.
Ren, Z., Wang, L., Cui, J., Huoc, Z., Xue, J., Hao, C., Mao, Q., & Yang, R. (2013) · PubMed · Cited by 138
Does calorie restriction induce mitochondrial biogenesis? A reevaluation
Hancock, C. R., Han, D., Higashida, K., Kim, S. H., & Holloszy, J. O. (2011) · The FASEB Journal · doi:10.1096/fj.10-170415 · Cited by 131 · cited 1×
“Similarly, Rsv, but not SIRT1 overexpression or CR, leads to a dramatic increase in skeletal muscle mitochondrial content [44,56,58].”
BackgroundNin, V., Escande, C., Chini, C. C. S., Giri, S., Camacho-Pereira, J., Matalonga, J., Lou, Z., & Chini, E. N. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.365874 · Cited by 123 · cited 2×
“According to it, AMPK would directly phosphorylate SIRT1 [84].”
BackgroundSIRT1 metabolic actions: Integrating recent advances from mouse models
Boutant, M., & Cantó, C. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.006 · Cited by 122 · cited 2×
“However, as discussed in a recent review [83], this mechanism might need further clarification given that previous reports failed to detect such phosphorylation event.”
BackgroundSelf-citationSirt1 activation by resveratrol is substrate sequence-selective
Lakshminarasimhan, M., Rauh, D., Schutkowski, M., & Steegborn, C. (2013) · Aging · doi:10.18632/aging.100542 · Cited by 120 · cited 1×
“with this, efforts from the Steegborn lab illustrated how Rsv action only triggers SIRT1-mediated deacetylation in a substrate specific fashion, and even led to a paradoxical inhibition of SIRT1 actions on certain substrates [51].”
BackgroundMercken, E. M., Hu, J. H., Krzysik-Walker, S. M., Wei, M., Li, Y., McBurney, M. W., de Cabo, R., & Longo, V. D. (2013) · Aging Cell · doi:10.1111/acel.12151 · Cited by 117
Resveratrol inhibits insulin responses in a SirT1-independent pathway
Zhang, J. (2006) · Biochemical Journal · doi:10.1042/bj20050977 · Cited by 115 · cited 1×
“IRS-1 and Grb2, which drives MAPK activation [119], although the genuine molecular mechanism was not identified in that case.”
BackgroundMinakawa, M., Miura, Y., & Yagasaki, K. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.05.017 · Cited by 114
Increased expression of Drosophila Sir 2 extends life span in a dose-dependent manner
Whitaker, R., Faulkner, S., Miyokawa, R., Burhenn, L., Henriksen, M., Wood, J. G., & Helfand, S. L. (2013) · Aging · doi:10.18632/aging.100599 · Cited by 106 · cited 1×
“Genetic manipulation of Sir2 orthologs was later demonstrated to affect lifespan in higher eukaryotes, such as nematodes [28, 29] and insects [30,31], even though the consistency and amplitude of this effect has been a matter of debate [32–34].”
BackgroundNarala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-09-0965 · Cited by 106
Miloso, M., Bertelli, A. A. E., Nicolini, G., & Tredici, G. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00194-9 · Cited by 101 · cited 1×
“For example, doses up to the lowmicromolar range might increase ERK signaling, whereas Rsv is inhibitory at the most commonly used, higher, doses (N50 μM) [133].”
BackgroundResveratrol Is a Potent Inhibitor of the Dioxygenase Activity of Lipoxygenase
Pinto, M. C., García-Barrado, J. A., & Macı́as, P. (1999) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf990448n · Cited by 97 · cited 1×
“In addition, Rsv has also been described to inhibit lipooxygenases (LOX) activity [102,103],”
BackgroundAdrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo
Pulinilkunnil, T., He, H., Kong, D., Asakura, K., Peroni, O. D., Lee, A. D., & Kahn, B. B. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.218719 · Cited by 85
Fukao, H., Ijiri, Y., Miura, M., Hashimoto, M., Yamashita, T., Fukunaga, C., Oiwa, K., Kawai, Y., Suwa, M., & Yamamoto, J. (2004) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-200408000-00001 · Cited by 68 · cited 1×
“Rsv effectively protected against plaque development in different animal models of atherogenesis [9,10].”
BackgroundTan, Z., Zhou, L., Mu, P., Liu, S., Chen, S., Fu, X., & Wang, T. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.12.003 · Cited by 67 · cited 1×
“In fact, while most data suggests that Rsv increases skeletal muscle glucose uptake [44,59,60], even in an acute fashion [61,62], SIRT1 transgenesis in the muscle does not affect insulin action [63].”
BackgroundLombard, D. B., Pletcher, S. D., Cantó, C., & Auwerx, J. H. (2011) · Nature · doi:10.1038/477410a · Cited by 47
Self-citationWhite, A. T., McCurdy, C. E., Philp, A., Hamilton, D. L., Johnson, C. D., & Schenk, S. (2013) · Diabetologia · doi:10.1007/s00125-013-2912-2 · Cited by 45 · cited 1×
“In fact, while most data suggests that Rsv increases skeletal muscle glucose uptake [44,59,60], even in an acute fashion [61,62], SIRT1 transgenesis in the muscle does not affect insulin action [63].”
BackgroundSirt1-Independent Mechanisms of the Putative Sirtuin Enzyme Activators SRT1720 and SRT2183
Huber, J. L., McBurney, M. W., DiStefano, P. S., & McDonagh, T. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.257 · Cited by 43
The pig as a valuable model for testing the effect of resveratrol to prevent cardiovascular disease
Elmadhun, N. Y., Sabe, A. A., Robich, M. P., Chu, L. M., Lassaletta, A. D., & Sellke, F. W. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12216 · Cited by 36 · cited 1×
“In porcine models, Rsv improved myocardial perfusion, and regional contractility while decreasing oxidative stress [13].”
BackgroundBertelli, A., Falchi, M., Dib, B., Pini, E., Mukherjee, S., & Das, D. K. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1926 · Cited by 25
Resveratrol Inhibits Protein Translation in Hepatic Cells
Villa-Cuesta, E., Boylan, J. M., Tatar, M., & Gruppuso, P. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029513 · Cited by 21 · cited 1×
“Recent studies have also demonstrated that Rsv inhibits mTOR signaling via a SIRT1-independent mechanism [122] and that it represses protein synthesis [123].”
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“Resveratrol has many targets, with some engaged at uM concentrations.(4) These findings suggest that a central molecular target may be engaged at nM concentrations.”
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Resveratrol (RV): A pharmacological review and call for further research
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Metadata
- Authors
- Kulkarni, S. S., & Cantó, C.
- Corresponding author
- Cantó, Carles
- ORCID
- Cantó, Carles
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 1852
- Issue
- 6
- Pages
- 1114-1123
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2053510668
- Cited by
- 477
- References
- 135
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 32 · 2023: 23 · 2022: 50 · 2021: 40 · 2020: 56 · 2019: 63 · 2018: 55 · 2017: 39 · 2016: 38 · 2015: 37
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- resveratrol, molecular targets, caloric restriction mimetics, SIRT1, AMPK, metabolic disorders, neuroprotection, cancer, cardioprotection, aging, drug development
- MeSH terms
- Resveratrol, Animals, Humans, Mitochondria, Stilbenes, Signal Transduction, Transcriptional Activation, NF-kappa B, Sirtuins, AMP-Activated Protein Kinases
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